Literature DB >> 14550297

Bax conformational change is a crucial step for PUMA-mediated apoptosis in human leukemia.

Feng-Ting Liu1, Adrian C Newland, Li Jia.   

Abstract

The BH3-only protein, PUMA, plays an important role in p53-mediated apoptosis. The apoptotic effect of PUMA on the mitochondria was studied using a p53-negative, human leukemia K562 cell line. Overexpression of PUMA was accompanied by an increased Bax expression, Bax conformational change, and translocation to mitochondria. A PUMA-BH3 peptide can induce Bax conformational change, cytochrome c release, and reduction in the mitochondrial membrane potential (DeltaPsi(m)) in isolated K562 mitochondria and can be inhibited by Bcl-XL. The homo-dimer of Bax/Bax was also weakly shown after mitochondria were treated with PUMA-BH3 peptide but may not be lethal for PUMA-induced apoptosis in K562 cells. Our results suggest that PUMA-induced Bax conformational change and Bax translocation to mitochondria can be separate events and the conformational change in Bax is crucial for PUMA-induced mitochondrial dysfunction.

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Year:  2003        PMID: 14550297     DOI: 10.1016/j.bbrc.2003.09.109

Source DB:  PubMed          Journal:  Biochem Biophys Res Commun        ISSN: 0006-291X            Impact factor:   3.575


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